Association of copeptin, a surrogate marker of arginine vasopressin, with cerebral vasospasm and delayed ischemic neurologic deficit after aneurysmal subarachnoid hemorrhage

OBJECTIVEDelayed ischemic neurological deficit (DIND) is a leading cause of mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Arginine vasopressin (AVP) is a hormone released by the posterior pituitary. It is known to cause cerebral vasoconstriction and has been implicated in hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Direct measurement of AVP is limited by its short half-life. Copeptin, a cleavage product of the AVP precursor protein, was therefore used as a surrogate marker for AVP. This study aimed to investigate the temporal relationship between changes in copeptin concentrations and episodes of DIND and hyponatremia.METHODSCopeptin concentrations in cerebrospinal fluid were quantified using enzyme-linked immunosorbent assay in 19 patients: 10 patients with DIND, 6 patients without DIND (no-DIND), and 3 controls.RESULTSCopeptin concentrations were higher in DIND and no-DIND patients than in controls. In hyponatremic DIND patients, copeptin concentrations were higher compared with hyponatremic no-DIND patients. DIND was associated with a combination of decreasing sodium levels and increasing copeptin concentrations.CONCLUSIONSIncreased AVP may be the unifying factor explaining the co-occurrence of hyponatremia and DIND. Future studies are indicated to investigate this relationship and the therapeutic utility of AVP antagonists in the clinical setting.

Microsurgical Vascular Manipulation in Aneurysm Surgery and Delayed Ischemic Injury

Background: The role of aggressive surgical manipulation with clot evacuation, arachnoid dissection, and papaverine-guided adventitial dissection of large vessels during ruptured aneurysm surgery in reducing vasospasm is controversial. Here we describe a single-institution experience in aneurysm surgery outcomes with and without aggressive surgery. Methods: We performed retrospective analysis of all patients >18 years of age with subarachnoid hemorrhage (SAH) from anterior circulation aneurysms between 2008 and 2013 at the University of New Mexico Hospital. Vasospasm was characterized on days 3 through 14 after SAH based on: (1) angiography, (2) vasospasm requiring angiographic intervention, (3) development of delayed ischemic neurologic deficit (DIND), and (4) radiological appearance of new strokes. Results: Of 159 patients, 114 (71.6%) had “aggressive” and 45 (28.3%) had standard microsurgery. More than 60% of patients presented with a Hunt and Hess score of ≥3 and a Fisher grade (FG) of 4. Compared with standard surgery, there was a statistically significant decrease in the incidence of DIND in patients undergoing aggressive surgery (18.4% vs 37.8%, p=0.01). Moreover, there was a reduction in the number of new strokes by 30% in the aggressive surgery group with moderate or higher degrees of vasospasm (46.0% vs 76.5%, p=0.06). In the same group with FG 4 SAH, however, this difference was more than 50% (30% vs 64.7%, p=0.02). Conclusions: We conclude that aggressive surgical manipulation during aneurysm surgery results in lower incidence of DIND and new strokes. This effect is most pronounced in patients with FG 4 SAH.

E.03 Use of intra-arterial milrinone rescue therapy in patients with refractory and super refractory vasospasm after aneurysmal subarachnoid hemorrhage

Background: Vasospasm causing delayed ischemic neurologic deficit (DIND) remains a leading cause of devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH). Therapy using intravenous milrinone (IVM) and intra-arterial milrinone (IAM) has been described. We report our results using IAM in patients with refractory and super refractory vasospasm (RV and SRV respectively). Methods: Retrospective single center study of all adult patients treated with IAM between 2006 and 2016 inclusively. IAM was used as part of the Montreal Neurological Hospital Protocol when the patients’ symptoms failed to respond to initial and higher IVM doses. We report their clinical outcomes. Results: IAM was used in 19 patients. The median loading dose was 8 mg and average maintenance dose was 0.78 mcg/kg/min. Angiographic improvement was seen in 15 (79%) and clinical improvement - within the first 48 hours - was seen in all patients. The median mRS was 3 at time of discharge and 1 three months later. Five patients lost follow up. Conclusions: IAM appears to be safe and effective in this small retrospective series of RV and SRV complicating aSAH. Angiographic and clinical improvements were observed. Further prospective studies are warranted to confirm these findings.

Medical Aspects of the Preoperative Management of Aneurysms: A Review

SUMMARY:The aim of medical management of a patient with a recently ruptured intracranial aneurysm is to preserve residual brain function and prevent systemic complications. Surgery should be performed as soon as the patient is in good neurological condition. Most fatalities result from the destructive effects of the initial hemorrhage, but delayed ischemic neurologic deficit can result from vasospasm and rebleeding. Systemic complications of the brain damaged state result in a smaller proportion of deaths.Common medical problems are reviewed as well as their medical management. In particular, some special problems related to subarachnoid hemorrhage such as cerebral edema and herniations, rebleeding, and vasospasm are also considered. Major recent advances have been the introduction of antifibrinolytic therapy, the realization of the importance of maintaining blood volume and pressure, as well as general advances in respiratory care.